Direct injection of cell-laden hydrogels shows high potential for tissue regeneration in translational therapy. The traditional cell-laden hydrogels are often used as bulk space fillers to tissue defects after injection, likely limiting their structural controllability. On the other hand, patterned cell-laden hydrogel constructs often necessitate invasive surgical procedures. To overcome these problems, herein, a unique strategy is reported for encapsulating living human cells in a pore-forming gelatin methacryloyl (GelMA)-based bioink to ultimately produce injectable hierarchically macro-micro-nanoporous cellladen GelMA hydrogel constructs through 3D extrusion bioprinting. The hydrogel constructs can be fabricated into various shapes and sizes that are defect-specific. Due to the hierarchically macro-micro-nanoporous structures, the cell-laden hydrogel constructs can readily recover to their original shapes, and sustain high cell viability, proliferation, spreading, and differentiation after compression and injection. In addition, in vivo studies further reveal that the hydrogel constructs can integrate well with the surrounding host tissues. These findings suggest that the unique 3D-bioprinted pore-forming GelMA hydrogel constructs are promising candidates for applications in minimally invasive tissue regeneration and cell therapy.

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The most common and malignant primary brain tumor in adults is glioblastoma (GBM). In vitro 3D brain models are needed to better understand the pathological processes underlying GBM and ultimately develop more efficient antineoplastic agents. Here, we describe the bioprinting methods that have been used to fabricate volumetric GBM models. We explain several factors that should be considered for 3D bioprinting, including bioinks, cells and construct designs, in relation to GBM modeling. Although 3D-bioprinted brain models are still to be improved, they have the potential to become a powerful tool for drug screening.